No indication for a defect in toll-like receptor signaling in patients with hyper-IgE syndrome.

Abstract

Hyper-IgE syndrome is a rare primary immunodeficiency of unknown etiology characterized by recurrent infections of the skin and respiratory system, chronic eczema, elevated total serum IgE, and a variety of associated skeletal symptoms. Recent reports about susceptibility to pyogenic bacterial infections and high IgE levels in patients and animals with defects in toll-like receptor (TLR) signaling pathways prompted us to search for TLR signaling defects as an underlying cause of hyper-IgE syndrome. Blood samples from six patients with hyper-IgE syndrome were analyzed for serum cytokine levels, intracellular cytokine production in T cells after stimulation with PMA/ionomycin, and cytokine production from peripheral blood mononuclear cells stimulated by TLR ligands and bacterial products including LPS (TLR4), peptidoglycan (TLR2), PolyIC (TLR3), R848 (TLR7/8), CpG-A, and CpG-B (TLR9), zymosan and heat killed Listeria monocytogenes. All results were compared to data from healthy controls. A reduction in IFN-gamma, IL-2, and TNF-alpha producing T cells after PMA stimulation suggested a reduced inflammatory T cell response in patients with hyper-IgE syndrome. Increased serum levels of IL-5 indicated a concomitant Th2 shift. However, normal production of cytokines (TNF-alpha, IL-6, IL-10, IFN-alpha, IP-10) and upregulation of CD86 on B cells and monocytes after TLR stimulation made a defect in TLR signaling pathways highly unlikely. In summary, our data confirmed an imbalance in T cell responses of patients with hyper-IgE syndrome as previously described but showed no indication for an underlying defect in toll-like receptor signaling.

• Authors: E D Renner, I Pawlita, F Hoffmann, V Hornung, D Hartl, M Albert, A Jansson, S Endres, G Hartmann, B H Belohradsky, S Rothenfusser
• Journal: Journal of clinical immunology (J Clin Immunol) Vol. 25 Issue 4 Pg. 321-8 (Jul 2005) ISSN: 0271-9142 [Print] Netherlands
• PMID: 16133988 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Ligands
• Toll-Like Receptors
• Immunoglobulin E

Topics

• Adolescent
• Adult
• Candidiasis (immunology)
• Child
• Child, Preschool
• Cytokines (biosynthesis, blood)
• Female
• Genetic Predisposition to Disease
• Humans
• Immunoglobulin E (biosynthesis, blood)
• Infant
• Job Syndrome (blood, immunology, microbiology)
• Ligands
• Male
• Signal Transduction (immunology)
• Staphylococcal Infections (immunology)
• T-Lymphocytes (immunology, metabolism)
• Toll-Like Receptors (metabolism, physiology)